Comparison of the replication and persistence of simian-human immunodeficiency viruses expressing Vif proteins with mutation of the SLQYLA or HCCH domains in macaques

Kimberly Schmitt, M. Sarah Hill, Zhenqian Liu, Autumn Schulze, Nathan Culley, David M. Pinson, Edward B. Stephens

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The Vif protein of primate lentiviruses interacts with APOBEC3 proteins, which results in shunting of the APOBEC3-Vif complex to the proteosome for degradation. Using the simian-human immunodeficiency virus (SHIV)/macaque model, we compared the replication and pathogenicity of SHIVs that express a Vif protein in which the entire SLQYLA (SHIVVif5A) or HCCH (SHIVVifHCCH(-)) domains were substituted with alanine residues. Each virus was inoculated into three macaques and various viral and immunological parameters followed for 6months. All macaques maintained stable circulating CD4+ T cells, developed low viral loads, maintained the engineered mutations, yielded no histological lesions, and developed immunoprecipitating antibodies early post-inoculation. Sequence analysis of nef and vpu from three lymphoid tissues revealed a high percentage of G-to-A-substitutions. Our results show that while the presence of HCCH and SLQYLA domains are critical in vivo, there may exist APOBEC3 negative reservoirs that allow for low levels of viral replication and persistence but not disease.

Original languageEnglish (US)
Pages (from-to)187-203
Number of pages17
JournalVirology
Volume404
Issue number2
DOIs
StatePublished - Sep 1 2010
Externally publishedYes

Fingerprint

Human Immunodeficiency Virus vif Gene Products
Simian Immunodeficiency Virus
vif Gene Products
Macaca
Mutation
Primate Lentiviruses
Lymphoid Tissue
Viral Load
Alanine
Sequence Analysis
Virulence
HIV
Viruses
T-Lymphocytes
Antibodies
Proteins

Keywords

  • APOBEC3F
  • APOBEC3G
  • BC box
  • Replication
  • Rhesus macaques
  • SHIV
  • Simian-human immunodeficiency virus
  • Vif
  • Zn binding motif

ASJC Scopus subject areas

  • Virology

Cite this

Comparison of the replication and persistence of simian-human immunodeficiency viruses expressing Vif proteins with mutation of the SLQYLA or HCCH domains in macaques. / Schmitt, Kimberly; Hill, M. Sarah; Liu, Zhenqian; Schulze, Autumn; Culley, Nathan; Pinson, David M.; Stephens, Edward B.

In: Virology, Vol. 404, No. 2, 01.09.2010, p. 187-203.

Research output: Contribution to journalArticle

Schmitt, Kimberly ; Hill, M. Sarah ; Liu, Zhenqian ; Schulze, Autumn ; Culley, Nathan ; Pinson, David M. ; Stephens, Edward B. / Comparison of the replication and persistence of simian-human immunodeficiency viruses expressing Vif proteins with mutation of the SLQYLA or HCCH domains in macaques. In: Virology. 2010 ; Vol. 404, No. 2. pp. 187-203.
@article{8258fd3d14124300bfb676a789d12f30,
title = "Comparison of the replication and persistence of simian-human immunodeficiency viruses expressing Vif proteins with mutation of the SLQYLA or HCCH domains in macaques",
abstract = "The Vif protein of primate lentiviruses interacts with APOBEC3 proteins, which results in shunting of the APOBEC3-Vif complex to the proteosome for degradation. Using the simian-human immunodeficiency virus (SHIV)/macaque model, we compared the replication and pathogenicity of SHIVs that express a Vif protein in which the entire SLQYLA (SHIVVif5A) or HCCH (SHIVVifHCCH(-)) domains were substituted with alanine residues. Each virus was inoculated into three macaques and various viral and immunological parameters followed for 6months. All macaques maintained stable circulating CD4+ T cells, developed low viral loads, maintained the engineered mutations, yielded no histological lesions, and developed immunoprecipitating antibodies early post-inoculation. Sequence analysis of nef and vpu from three lymphoid tissues revealed a high percentage of G-to-A-substitutions. Our results show that while the presence of HCCH and SLQYLA domains are critical in vivo, there may exist APOBEC3 negative reservoirs that allow for low levels of viral replication and persistence but not disease.",
keywords = "APOBEC3F, APOBEC3G, BC box, Replication, Rhesus macaques, SHIV, Simian-human immunodeficiency virus, Vif, Zn binding motif",
author = "Kimberly Schmitt and Hill, {M. Sarah} and Zhenqian Liu and Autumn Schulze and Nathan Culley and Pinson, {David M.} and Stephens, {Edward B.}",
year = "2010",
month = "9",
day = "1",
doi = "10.1016/j.virol.2010.04.017",
language = "English (US)",
volume = "404",
pages = "187--203",
journal = "Virology",
issn = "0042-6822",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Comparison of the replication and persistence of simian-human immunodeficiency viruses expressing Vif proteins with mutation of the SLQYLA or HCCH domains in macaques

AU - Schmitt, Kimberly

AU - Hill, M. Sarah

AU - Liu, Zhenqian

AU - Schulze, Autumn

AU - Culley, Nathan

AU - Pinson, David M.

AU - Stephens, Edward B.

PY - 2010/9/1

Y1 - 2010/9/1

N2 - The Vif protein of primate lentiviruses interacts with APOBEC3 proteins, which results in shunting of the APOBEC3-Vif complex to the proteosome for degradation. Using the simian-human immunodeficiency virus (SHIV)/macaque model, we compared the replication and pathogenicity of SHIVs that express a Vif protein in which the entire SLQYLA (SHIVVif5A) or HCCH (SHIVVifHCCH(-)) domains were substituted with alanine residues. Each virus was inoculated into three macaques and various viral and immunological parameters followed for 6months. All macaques maintained stable circulating CD4+ T cells, developed low viral loads, maintained the engineered mutations, yielded no histological lesions, and developed immunoprecipitating antibodies early post-inoculation. Sequence analysis of nef and vpu from three lymphoid tissues revealed a high percentage of G-to-A-substitutions. Our results show that while the presence of HCCH and SLQYLA domains are critical in vivo, there may exist APOBEC3 negative reservoirs that allow for low levels of viral replication and persistence but not disease.

AB - The Vif protein of primate lentiviruses interacts with APOBEC3 proteins, which results in shunting of the APOBEC3-Vif complex to the proteosome for degradation. Using the simian-human immunodeficiency virus (SHIV)/macaque model, we compared the replication and pathogenicity of SHIVs that express a Vif protein in which the entire SLQYLA (SHIVVif5A) or HCCH (SHIVVifHCCH(-)) domains were substituted with alanine residues. Each virus was inoculated into three macaques and various viral and immunological parameters followed for 6months. All macaques maintained stable circulating CD4+ T cells, developed low viral loads, maintained the engineered mutations, yielded no histological lesions, and developed immunoprecipitating antibodies early post-inoculation. Sequence analysis of nef and vpu from three lymphoid tissues revealed a high percentage of G-to-A-substitutions. Our results show that while the presence of HCCH and SLQYLA domains are critical in vivo, there may exist APOBEC3 negative reservoirs that allow for low levels of viral replication and persistence but not disease.

KW - APOBEC3F

KW - APOBEC3G

KW - BC box

KW - Replication

KW - Rhesus macaques

KW - SHIV

KW - Simian-human immunodeficiency virus

KW - Vif

KW - Zn binding motif

UR - http://www.scopus.com/inward/record.url?scp=77954535463&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77954535463&partnerID=8YFLogxK

U2 - 10.1016/j.virol.2010.04.017

DO - 10.1016/j.virol.2010.04.017

M3 - Article

VL - 404

SP - 187

EP - 203

JO - Virology

JF - Virology

SN - 0042-6822

IS - 2

ER -